The C.sub.20 unsaturated fatty acids, known as prostaglandins, form a large family of naturally-occurring compounds. Their structure, biological activities and medicinal use have been variously described in U.S. Pat. Nos. 3,971,826, 3,984,400 and in application Ser. No. 727,463, now abandoned.
One of the principal goals guiding the preparation of synthetic pharmaceutical agents is the development of compounds which are highly selective in their pharmacological activity and which have an increased duration of activity over their naturally-occurring congeners. In a series of compounds similar to the naturally-occurring prostaglandins, increasing selectivity of a single compound usually involves enhancement of one prostaglandin-like physiological effect and the diminution of the others. The potential benefits of this selectivity are manifold; e.g., a decrease in the severe side effects such as diarrhea and emesis which are frequently observed following administration of the natural prostaglandins. A separation of cardiovascular and bronchodilator activity which are both embraced by natural prostaglandins also would have obvious medicinal potential. Recent developments directed toward an increase of biological selectivity include the 16,16-dimethyl prostaglandins [B. J. Magerkin, et al., Prostaglandins, 4, 143 (1973)], 17-oxaprostaglandin F.sub.2 .alpha.[J. Bowler, et al., Prostaglandins, 9, 391 (1975); 10, 5 (1975)], 16,16-dialkyl (including dimethyl)-17, 18 or 19-oxaprostaglandin E.sub.2, E.sub.1, F.sub.2.alpha., F.sub. 1.alpha. ; the 11, 15-bis- THP ethers of those compounds; [Belgium 827,529]; 16,16-dimethyl-17-oxaprostaglandin E.sub.2, E.sub.1, F.sub.2.alpha. F.sub.1.alpha. and the 11,15-bis THP ethers of those compounds [Belgium 832,479] and N-substituted prostaglandin carboxamides including N-alkylsulfonyl, N-alkanoyl and N-benzoyl PGE.sub.2 and PGE.sub.2.alpha. carboxamides [U.S. 3,954,741].